Prognosis in clinical cancer is an area of great concern and interest. It is important to know the aggressiveness of malignant cells and the likelihood of tumor recurrence or spread in order to plan the most effective therapy. Certain cancers are managed by alternative strategies. In some cases local-regional therapy is utilized, while in other cases when spread of disease is detected or suspected, systemic therapy is instituted.
Inactivation of tumor suppression genes is an important event contributing to the development of neoplastic malignancies. In addition to the classical genetic mechanisms involving deletions or activating point mutations, growth regulatory genes can be functionally inactivated or otherwise modulated by epigenetic alterations. These may involve alterations in the genome other than the DNA sequence itself, which include genomic hypomethylations, promoter-related hypermethylation (e.g., of CpG dinucleotides, and CpG islands), histone deacetylation and chromatin modifications. Molecular analysis of tumor-derived genetic and epigenetic alterations may have a profound impact on cancer diagnosis and monitoring for tumor recurrence.
DNA methylation is a naturally-occurring epigenetic modification that occurs in a cytosine base followed by a guanosine base (CpG). In general, CpG hypermethylation is thought to be associated with transcriptional silencing. It is believed that methylation can result in recruitment of methylation binding proteins (MBPs) and histone deacetylation of, for example, tumor suppressor genes, inactivating them and allowing tumors to form.
A need exists in the art for methods and tests that provide predictive information about patient prognosis and likelihood of survival. More particularly, methods are needed for identifying and statistically correlating altered gene expression with a specific stage of cancer.